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FUNCTIONAL DYSPEPSIA Manoon M. 3/9/20 Update management for general practice
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  • FUNCTIONAL DYSPEPSIA

    Manoon M.

    3/9/20

    Update management for general practice

  • Outline

    • Dyspepsia

    • Uninvestigated dyspepsia (UD)

    • Functional dyspepsia (FD)

    • Alarm symptoms

    • Esophagogastroscopy (EGD)

    • Treatment for FD

  • DYSPEPSIA

    •A heterogeneous group of symptoms (pain or discomfort) in the upper abdomen without alarm symptoms for at least 4 weeks.

    Thailand Dyspepsia Guidelines 2018

  • Dyspeptic symptoms

    Epigastric pain or burning Belching*

    Sensation of fullness Nausea and vomiting

    Early satiation Upper abdominal bloating

    Anorexia Heartburn and regurgitation

    * the most common manifestation in Asian countries

    Thailand Dyspepsia Guidelines 2018

  • Organic causes of dyspepsia LUMINAL GI TRACT PANCREATICOBILIARY DISORDERS

    • Chronic gastric volvulus • Chronic gastric or intestinal ischemia • Food intolerance • Gastric infections (CMV, fungus, tuberculosis,

    syphilis) • Gastric or esophageal neoplasms • Gastroesophageal reflux disease • Gastroparesis (diabetes mellitus, postvagotomy,

    scleroderma, chronic intestinal pseudo-obstruction, postviral, idiopathic)

    • Irritable bowel syndrome • Infiltrative gastric disorders (Ménétrier disease,

    Crohn disease, eosinophilic gastroenteritis, sarcoidosis, amyloidosis)

    • Parasites (Giardia lamblia, Strongyloides stercoralisrom)

    • Peptic ulcer disease

    • Biliary pain: cholelithiasis, choledocholithiasis, SOD

    • Chronic pancreatitis • Pancreatic neoplasms

    SYSTEMIC CONDITIONS

    • Adrenal insufficiency • Diabetes mellitus • Heart failure • Hyperparathyroidism • Intra-abdominal malignancy • Myocardial ischemia • Pregnancy • Renal insufficiency • Thyroid disease

    Sleisenger and Fordtran’s 11th ed,2021

  • MEDICATIONS

    • Acarbose • Alcohol • Antibiotics, oral (e.g., erythromycin, penicillin,

    macrolides) • Aspirin, NSAIDs (including COX-2 selective agents) • Bisphosphonates • CCBs • Colchicine • Corticosteroids • Digitalis preparations • Estrogens • Herbs (e.g., garlic, ginkgo, saw palmetto, feverfew,

    chaste tree berry, white willow)

    • Iron • Potassium chloride • Levodopa • Metformin • Narcotics • Niacin • Gemfibrozil • Nitrates • Opiates • Orlistat • Quinidine • Sildenafil • Theophylline

    Adapted from Loyd RA & McClellan DA .Am Fam Physician 2011 Mar 1;83(5):547-52 Talley NJ, Ford AC. N EnglJ Med 2015;373:1853-63

    Sleisenger and Fordtran’s 11th ed,2021

  • Dyspepsia ควรส่งตรวจเพิม่เติม เม่ือไหร่? ไม่เคยเป็นมาก่อน - อาการเขา้ไดก้บัdyspepsia? สาเหตทุี่ซกัประวตัิพบ? มีตวัตาเหลือง? มีความเสี่ยงโรคหวัใจขาดเลือด? ถา้ไมช่ดัเจนควรตรวจเพิ่มเติม

    เคยเป็นมาก่อน รกัษาแลว้ดีขึน้ - อาการเหมือนเดิม? สาเหตเุหมือนเดิม? มีการใชย้าตวัใหม่ๆ/อาหาร/เครือ่งดื่มที่อาจเป็นสาเหต?ุ มีalarm symptomsไหม? รกัษาแลว้ไมด่ีขึน้ - เหมือนกลุม่เคยรกัษาแลว้ดีขึน้ และ ประเมินวา่ใหย้าขนาดเหมาะสมแลว้หรอืไม ่ใหม้านานแค่ไหนแลว้ เคยสง่ตรวจทางหอ้งปฏิบตัิการ/อลัตรา้ซาวดช์่องทอ้งบา้งหรอืไม ่

  • UNINVESTIGATED DYSPEPSIA (UD)

    • Dyspeptic symptoms in people who have not yet undergone specific diagnostic investigations.

    Thailand Dyspepsia Guidelines 2018

  • FUNCTIONAL DYSPEPSIA (FD)

    • Dyspeptic symptoms cannot be explained by a routine clinical evaluation, including endoscopy, and there is no evidence of Helicobacter pylori infection.

    • 2 subcategories:

    (1) Postprandial distress syndrome

    Postprandial fullness and early satiation (related to meal).

    (2) Epigastric pain syndrome

    Epigastric pain and epigastric burning (not related to meals).

    Thailand Dyspepsia Guidelines 2018

  • FUNCTIONAL DYSPEPSIA (FD)

    • The worldwide prevalence of UD varies from 7% to 34%, with a pooled UD prevalence from 21 Southeast Asian studies of 21.6%.

    • In Asian populations, the risk of malignancy associated with UD is approximately 1.3% (95% CI, 0.80-2.10).

    • Secondary dyspepsia was identified in 18% of UD patients after undergoing an endoscopy in Asian countries.

    • In Thailand, 60-90% of patients with dyspepsia are eventually diagnosed with FD

    • FD is a benign but chronic condition that often fluctuates and is sometimes recurrent.

    Thailand Dyspepsia Guidelines 2018

  • ALARM FEATURES

    • Evidence of upper GI bleeding hematemesis, melena, maroon stool, or iron deficiency without other causes.

    • Early satiety.

    • Unexplained weight loss (>10% body weight).

    • Persistent vomiting due to an unknown cause (defined as vomiting > 10 times in 24 hours or vomiting after each meal).

    • Family history of upper GI cancer in a first-degree relative.

    Thailand Dyspepsia Guidelines 2018

  • ESOPHAGOGASTRODUODENOSCOPY (EGD)

    • Dyspeptic patients who have 1 of the following: (1) Age of onset of 50 years or older (2) Alarm features (3) Symptoms are non-responsive to a trial of appropriate medical therapy.

    Thailand Dyspepsia Guidelines 2018

  • GERD Dyspepsia

    (Duration ≥ 4 weeks)

    Uninvestigated Investigated

    Organic

    18%

    PUD 11%

    Erosive esophagitis 6%

    Malignancy 1%

    Functional

    60-90%

    Postprandial distress

    syndrome

    Epigastric pain syndrome

    Alarm symptoms

    1) UGIB

    2) Early satiety

    3) Weight loss (>10%)

    4) Vomiting > 10 times in 24 hours or vomiting after each meal

    5) Family history of upper GI cancer in a first-degree relative

    IBS

    Thailand Dyspepsia Guidelines 2018 StanghelliniV., et al. Gastroenterology. 2016 May;150(6):1380-92

  • Rome IV Criteria for Functional Dyspepsia • Presence of 1 symptom(s) of postprandial fullness, early satiety, epigastric pain, or epigastric burning • No evidence of structural disease that could explain the symptoms

    PDS (38%) Postprandial fullness or early satiety 3 days/week for the past 3 months and onset 6 months before diagnosis

    EPS (27%) Epigastric pain and/or burning 1 day(s)/week for the past 3 months and onset 6 months before diagnosis

    Overlap PDS/EPS 35% Drossman DA, Hasler WL. Gastroenterology. 2016;150(6):1257-1261.

  • Talley NJ. Korean J Intern Med 2016

    Etiology of Functional Dyspepsia

  • TREATMENT OF FUNCTIONAL DYSPEPSIA

  • Treatment modalities

    • Pharmacotherapy • Acid-Reducing Therapy • Neuromodulators • Prokinetics and Fundus-Relaxing Therapies

    • Complementary and Alternative Medicine

    • Psychological Therapies

    • Helicobacter pylori Eradication

    Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020

  • Pharmacotherapy Treatment Therapeutic efficacy Quality of

    evidence

    PPIs Therapeutic gain 7-10% NNT 10-13 Mod

    H2RA Therapeutic gain 8-35% NNT 7-13 Low/mod

    Prokinetics Therapeutic gain 18-45% NNT 6-7 Low

    TCAs, antipsychotics Response rates 64-70% NNT 6 NNH 21

    Low

    Rebamipide Better than placebo SMD -0.62 Low

    SSRI/SNRI = Placebo NNH 6-16 Very low

    Antacid, bismuth, sucralfate

    = Placebo NA Very low

    Lacy BE, et al. Aliment Pharmacol Ther 2012;36:3-15 Ford AC, et al. Gut 2017;66:411-20 Jaafar MH, et al. Dig Dis Sci 2018;63:1250-60

    Pinto-Sanchez MI, et al. Cochrane Database Syst Rev 2008 Pittayanon R, et al. Am J Gastroenterol 2018;114:233-243

    Moayyedi PM, et al. ACG Guideline 2017

  • Neuromodulators

    • Sulpiride

    • Levosulpiride

    • Mirtazapine

    • Tricyclic antidepressants (TCAs) • Amitriptyline and imipramine

    *** Not nortriptyline, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNSIs).

    Ford AC, et al. Gut 2017;66:411-420 Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020

  • Serotonin Receptor agonist

    Pro-kinetic Drug

    D2 Receptor antagonist

    - Metoclopramide* - Cisapride - Mosapride

    - Domperidone - Itopride

    * Metoclopramide: action both serotonin agonist and D2 antagonist

  • Prokinetic agents in Thailand Metoclopramide (Plasil)

    Domperidone (Motilium)

    Itopride (Ganaton)

    Mosapride (Gasmotin)

    Mode of action D2 antagonist (5HT4 agonist ) (5HT3 antagonist)

    D2 antagonist

    D2 antagonist AChE inhibitor

    5HT4 agonist

    Metabolism pathway CYP450 CYP450 FMO3 CYP450

    Prokinetic effects Strong Moderate Strong Strong

    Antiemetic effects Strong Moderate-strong Moderate None

    QT prolong - + - A case report

    Prolactin elevation Rare-moderate Rare-moderate Rare Rare

    EPS effects Frequent Rare Rare Rare

    Organ selectivity Upper gut Upper gut Upper gut (lower?) Upper and lower gut

  • ให้ยาอย่างไร? เม่ือไหร่? เรียกว่าตอบสนองหรือไม่ได้ผล

    Thailand Dyspepsia Guidelines 2018

  • ให้ยาอย่างไร? เม่ือไหร่? เรียกว่าตอบสนองหรือไม่ได้ผล

    Thailand Dyspepsia Guidelines 2018

    Omeprazole 20-40mg/day 4-8 weeks

    Domperidone 10mg tid or qid ac Mosapride 5mg tid ac

    Amitriptyline 25-50 mg/day

    Rebamipide 100mg tid ac

  • Refractory functional dyspepsia

    • FD that has continuous symptoms for at least 8 weeks and has been unresponsive to at least 2 medical treatments.*

    • The guidelines for FD in the Asia-Pacific region and the United States of America (USA) recommend changing to a different drug if adequate therapeutic efficacy has not been achieved after 4 weeks of treatment.

    * Miwa H. et al. J Gastroenterol 2015;50:125-139.

  • Management of Refractory FD

    • H2-RA if PPIs have failed.

    • Combination of acid suppression with a prokinetic agent.

    • Combination of drug therapy with psychological treatment.

    • Adjusting the dose of a TCA, prescribing an antipsychotic drug such as levosulpiride, or adding an anxiolytic.

    • The combination of an antidepressant with pregabalin or gabapentin is yet another option that appears to relieve pain.

    • Opioids have no therapeutic role and should be avoided because of the risk of dependence.

    Neurogastroenterol Motil 2015; 27: 455-67 Am J Gastroenterol 2014; 2: 22-30

  • หยุดยาได้ไหม?

    Thailand Dyspepsia Guidelines 2018

  • หยุดยาได้ไหม?

    ถ้าอาการดขีึน้ ค่อยๆลดยาลง เช่น จาก Multiple drugs single drug

    BID dose OD dose วันเว้น1-2วัน เฉพาะเวลามอีาการ

    ภายใน 6-12 เดอืน

    Thailand Dyspepsia Guidelines 2018

  • โรคนีจ้ะหายไหม?

    • All FD patients should be offered a positive diagnosis after targeted investigation

    • Attention to stress reduction and lowering of anxiety is important

    50% Resolution of symptoms

    30-35% Symptoms fluctuate and/or meet criteria for another FGIDs

    15-20% Persistent symptoms

    No evidence to suggest that it is associated with decreased survival

    Talley NJ, Ford AC. N Engl J Med 2015;373:1853-63

  • อยู่ รพช. เม่ือไหร่? ควรส่งต่อพบแพทย์เฉพาะทาง

    Thailand Dyspepsia Guidelines 2018

  • อยู่ รพช. ควรส่งต่อพบแพทย์เฉพาะทางเม่ือไหร่?

    Thailand Dyspepsia Guidelines 2018

  • ห้าม/แนะน าการรับประทานอาหาร,เคร่ืองด่ืมอย่างไรบ้าง?

    Dietary recommendations for patients with functional dyspepsia.

    • Eat slowly and regularly.

    • Decrease fat intake.

    • Try to observe a diet that is more similar to a Mediterranean diet or increase

    the intake of fresh foods and decrease the intake of ultra-processed foods.

    • Decrease coffee and alcohol consumption.

    • A gluten-free diet and a low-FODMAPs diet could be tested over a short time

    period (4–8 weeks) and must be stopped if there is no efficacy.

    • Be careful in providing strong recommendations to obsessive patients, and

    avoid the recommendation of very restrictive diets.

    Duboc et al. Front. Psychiatry, 05 February 2020

  • ห้าม/แนะน าการรับประทานอาหาร,เคร่ืองด่ืมอย่างไรบ้าง?

    Dietary recommendations for patients with functional dyspepsia.

    • Eat slowly and regularly.

    • Decrease fat intake.

    • Try to observe a diet that is more similar to a Mediterranean diet or increase

    the intake of fresh foods and decrease the intake of ultra-processed foods.

    • Decrease coffee and alcohol consumption.

    • A gluten-free diet and a low-FODMAPs diet could be tested over a short time

    period (4–8 weeks) and must be stopped if there is no efficacy.

    • Be careful in providing strong recommendations to obsessive patients, and

    avoid the recommendation of very restrictive diets.

    Duboc et al. Front. Psychiatry, 05 February 2020

    รับประทานช้าๆ เนือ้สัตวไ์ม่ผ่านการปรุงแต่ง เน้นผักผลไม้ ไม่มัน ไม่หวาน ไม่หมักดอง งดกาแฟและแอลกอฮอล ์

  • สมุนไพร/อาหารเสริม ท่ีช่วยใหดี้ข้ึนมีไหม?

    • Peppermint

    • Ginger (ขิง)

    • STW5

    • FDgard

    • Turmeric (ขมิน้ชนั)

  • THANK YOU